scholarly journals A model of the enteric neural circuitry underlying the generation of rhythmic motor patterns in the colon: the role of serotonin

2017 ◽  
Vol 312 (1) ◽  
pp. G1-G14 ◽  
Author(s):  
Terence Keith Smith ◽  
Sang Don Koh

We discuss the role of multiple cell types involved in rhythmic motor patterns in the large intestine that include tonic inhibition of the muscle layers interrupted by rhythmic colonic migrating motor complexes (CMMCs) and secretomotor activity. We propose a model that assumes these motor patterns are dependent on myenteric descending 5-hydroxytryptamine (5-HT, serotonin) interneurons. Asynchronous firing in 5-HT neurons excite inhibitory motor neurons (IMNs) to generate tonic inhibition occurring between CMMCs. IMNs release mainly nitric oxide (NO) to inhibit the muscle, intrinsic primary afferent neurons (IPANs), glial cells, and pacemaker myenteric pacemaker interstitial cells of Cajal (ICC-MY). Mucosal release of 5-HT from enterochromaffin (EC) cells excites the mucosal endings of IPANs that synapse with 5-HT descending interneurons and perhaps ascending interneurons, thereby coupling EC cell 5-HT to myenteric 5-HT neurons, synchronizing their activity. Synchronized 5-HT neurons generate a slow excitatory postsynaptic potential in IPANs via 5-HT7 receptors and excite glial cells and ascending excitatory nerve pathways that are normally inhibited by NO. Excited glial cells release prostaglandins to inhibit IMNs (disinhibition) to allow full excitation of ICC-MY and muscle by excitatory motor neurons (EMNs). EMNs release ACh and tachykinins to excite pacemaker ICC-MY and muscle, leading to the simultaneous contraction of both the longitudinal and circular muscle layers. Myenteric 5-HT neurons also project to the submucous plexus to couple motility with secretion, especially during a CMMC. Glial cells are necessary for switching between different colonic motor behaviors. This model emphasizes the importance of myenteric 5-HT neurons and the likely consequence of their coupling and uncoupling to mucosal 5-HT by IPANs during colonic motor behaviors.

2015 ◽  
Vol 114 (3) ◽  
pp. 1677-1692 ◽  
Author(s):  
Albert W. Hamood ◽  
Eve Marder

For decades, the episodic gastric rhythm of the crustacean stomatogastric nervous system (STNS) has served as an important model system for understanding the generation of rhythmic motor behaviors. Here we quantitatively describe many features of the gastric rhythm of the crab Cancer borealis under several conditions. First, we analyzed spontaneous gastric rhythms produced by freshly dissected preparations of the STNS, including the cycle frequency and phase relationships among gastric units. We find that phase is relatively conserved across frequency, similar to the pyloric rhythm. We also describe relationships between these two rhythms, including a significant gastric/pyloric frequency correlation. We then performed continuous, days-long extracellular recordings of gastric activity from preparations of the STNS in which neuromodulatory inputs to the stomatogastric ganglion were left intact and also from preparations in which these modulatory inputs were cut (decentralization). This allowed us to provide quantitative descriptions of variability and phase conservation within preparations across time. For intact preparations, gastric activity was more variable than pyloric activity but remained relatively stable across 4–6 days, and many significant correlations were found between phase and frequency within animals. Decentralized preparations displayed fewer episodes of gastric activity, with altered phase relationships, lower frequencies, and reduced coordination both among gastric units and between the gastric and pyloric rhythms. Together, these results provide insight into the role of neuromodulation in episodic pattern generation and the extent of animal-to-animal variability in features of spontaneously occurring gastric rhythms.


2003 ◽  
Vol 284 (2) ◽  
pp. G231-G241 ◽  
Author(s):  
Nick J. Spencer ◽  
Grant W. Hennig ◽  
Terence K. Smith

The role of the longitudinal muscle (LM) layer during the peristaltic reflex in the small and large intestine is unclear. In this study, we have made double and quadruple simultaneous intracellular recordings from LM and circular muscle (CM) cells of guinea pig distal colon to correlate the electrical activities in the two different muscle layers during circumferential stretch. Simultaneous recordings from LM and CM cells (<200 μm apart) at the oral region of the colon showed that excitatory junction potentials (EJPs) discharged synchronously in both muscle layers for periods of up to 6 h. Similarly, at the anal region of the colon, inhibitory junction potentials (IJPs) discharged synchronously in the two muscle layers. Quadruple recordings from LM and CM orally at the same time as from the LM and CM anally revealed that IJPs occurred synchronously in the LM and CM anally at the same time as EJPs in LM and CM located 20 mm orally. Oral EJPs and anal IJPs were linearly related in amplitude between the two muscle layers. Spatiotemporal maps generated from simultaneous video imaging of the movements of the colon, combined with intracellular recordings, revealed that some LM contractions orally could be correlated in time with IJPs in CM cells anally. N ω-nitro-l-arginine (l-NA; 100 μM) abolished the IJP in LM, whereas a prominent l-NA-resistant “fast” IJP was always observed in CM. In summary, in stretched preparations, synchronized EJPs in both LM and CM orally are generated by synchronized firing of many ascending interneurons, which simultaneously activate excitatory motor neurons to both muscle layers. Similarly, synchronized IJPs in both LM and CM anally are generated by synchronized firing of many descending interneurons, which simultaneously activate inhibitory motor neurons to both muscle layers. This synchronized motor activity ensures that both muscles around the entire circumference are excited orally at the same time as inhibited anally, thus producing net aboral propulsion.


1993 ◽  
Vol 264 (6) ◽  
pp. G1024-G1030 ◽  
Author(s):  
R. W. Summers ◽  
B. Hayek

The purpose of the study was to compare colonic motor patterns before and after a single abdominal dose of X-rays in dogs. Recordings were made from five serosally implanted strain gauges at equidistant intervals along the colon in seven dogs (2 dogs also had 2 jejunal electrodes and 1 had ileal electrodes). Control recordings were made for 3 h in the fasted state and daily for 2 wk after an absorbed X-ray dose of 938 cGy was delivered to the abdomen. The duration of migrating colonic motor complexes decreased from 7.2 +/- 0.5 to 3.9 +/- 0.4 min while the mean amplitude fell from 10.3 +/- 0.6 to 1.8 +/- 0.2 g (P < 0.05). The rate of nonmigrating colonic motor complex occurrence increased from 0.6 +/- 0.1 to 1.2 +/- 0.2 per hour (P < 0.05). Colonic giant migrating contractions were rarely observed during control recordings (2 in 80 h of recording). In contrast, repetitive clusters of giant contractions were observed 5-8 days after exposure in five of seven dogs (1.5/h) and were associated with restlessness, whining, and passage of diarrheal stools (sometimes bloody) with nearly every occurrence. The basic colonic motility patterns were less disrupted than were jejunal myoelectric patterns at the same irradiation dosage. However, the study demonstrates the important role of colonic giant migrating contractions in pathological diarrheal states such as irradiation injury.


1987 ◽  
Vol 253 (2) ◽  
pp. G226-G231 ◽  
Author(s):  
J. R. Grider ◽  
G. M. Makhlouf

The participation of opioid neurons in the regulation of peristalsis was examined in a rat colonic segment that permits separate characterization of the components of the peristaltic reflex (ascending contraction and descending relaxation). Naloxone increased descending relaxation and decreased ascending contraction; opioid peptides [methionine-enkephalin (Met-Enk), dynorphin-13, and morphiceptin] had opposite effects. Naloxone increased, and Met-Enk decreased, vasoactive intestinal peptide (VIP) release during each component of the reflex. The changes in VIP release reinforced the direct effects of naloxone and opioid peptides on circular muscle tone, providing an explanation for the effects of these agents on the two components of the peristaltic reflex. Dynorphin release decreased during descending relaxation and increased during ascending contraction, reflecting corresponding changes in opioid neural activity. Based on these results a model is proposed, according to which a decrease in opioid neural activity during the initial phase (i.e., descending relaxation) results in direct and VIP-mediated decrease in circular muscle tone. Restoration of opioid neural activity during the subsequent phase (i.e., ascending contraction) increases circular muscle tone and reinforces the action of tachykinin and cholinergic motor neurons, which are the direct mediators of ascending contraction.


Author(s):  
Jan D. Huizinga ◽  
Amer Hussain ◽  
Ji-Hong Chen

Our understanding of human colonic motility, and autonomic reflexes that generate motor patterns, has increased markedly through high-resolution manometry. Details of the motor patterns are emerging related to frequency and propagation characteristics that allow linkage to interstitial cells of Cajal (ICC) networks. In studies on colonic motor dysfunction requiring surgery, ICC are almost always abnormal or significantly reduced. However, there are still gaps in our knowledge about the role of ICC in the control of colonic motility and there is little understanding of a mechanistic link between ICC abnormalities and colonic motor dysfunction. This review will outline the various ICC networks in the human colon and their proven and likely associations with the enteric and extrinsic autonomic nervous systems. Based on our extensive knowledge of the role of ICC in the control of gastrointestinal motility of animal models and the human stomach and small intestine, we propose how ICC networks are underlying the motor patterns of the human colon. The role of ICC will be reviewed in the autonomic neural reflexes that evoke essential motor patterns for transit and defecation. Mechanisms underlying ICC injury, maintenance, and repair will be discussed. Hypotheses are formulated as to how ICC dysfunction can lead to motor abnormalities in slow transit constipation, chronic idiopathic pseudo-obstruction, Hirschsprung's disease, fecal incontinence, diverticular disease, and inflammatory conditions. Recent studies on ICC repair after injury hold promise for future therapies.


1986 ◽  
Vol 55 (4) ◽  
pp. 678-688 ◽  
Author(s):  
K. T. Sillar ◽  
P. Skorupski

A preparation is described in which the thoracic ganglia of the crayfish are isolated together with the thoracocoxal muscle receptor organ (TCMRO) of the fourth leg. This preparation allows intracellular analysis of both centrally generated and reflex activity in leg motor neurons (MNs). The isolated thoracic ganglia can spontaneously generate a rhythmic motor pattern resembling that used during forward walking (Fig. 4). This involves the reciprocal activity of promotor and remotor MNs, with levator MNs firing in phase with promotor bursts. Stretch of the TCMRO in quiescent preparations evokes a resistance reflex in promotor MNs (Fig. 6). In more active preparations the response is variable and often becomes an assistance reflex, with excitation of remotor MNs on stretch (Fig. 7). When rhythmic motor patterns occur, the neuropilar processes of the S and T fibers receive central inputs that are strongly correlated with the oscillatory drive to the MNs and probably have the same origin (Figs. 8 and 9). Central inputs to the S and T fibers occur in opposite phases within a cycle of rhythmic motor output. The S fiber is depolarized in phase with promotor MNs and the T fiber in phase with remotor activity. The input to the T fiber is shown to be a chemical synaptic drive that has a reversal potential approximately 14 mV more depolarized than the fiber's resting membrane potential. This input substantially modulates the amplitude and waveform of passively propagated receptor potentials generated by TCMRO stretch (Fig. 11). It is argued that the central inputs to the TCMRO afferents will modulate proprioceptive feedback resulting from voluntary movements.


Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 100
Author(s):  
Alexandra Proshchina ◽  
Victoria Gulimova ◽  
Anastasia Kharlamova ◽  
Yuliya Krivova ◽  
Valeriy Barabanov ◽  
...  

Spaceflight may cause hypogravitational motor syndrome (HMS). However, the role of the nervous system in the formation of HMS remains poorly understood. The aim of this study was to estimate the effects of space flights on the cytoskeleton of the neuronal and glial cells in the spinal cord and mechanoreceptors in the toes of thick-toed geckos (Chondrodactylus turneri GRAY, 1864). Thick-toed geckos are able to maintain attachment and natural locomotion in weightlessness. Different types of mechanoreceptors have been described in the toes of geckos. After flight, neurofilament 200 immunoreactivity in mechanoreceptors was lower than in control. In some motor neurons of flight geckos, nonspecific pathomorphological changes were observed, but they were also detected in the control. No signs of gliosis were detected after spaceflight. Cytoskeleton markers adequately reflect changes in the cells of the nervous system. We suggest that geckos’ adhesion is controlled by the nervous system. Our study revealed no significant disturbances in the morphology of the spinal cord after the prolonged space flight, supporting the hypothesis that geckos compensate the alterations, characteristic for other mammals in weightlessness, by tactile stimulation.


1992 ◽  
Vol 68 (5) ◽  
pp. 1693-1707 ◽  
Author(s):  
G. Wittenberg ◽  
W. B. Kristan

1. Mechanical stimulation of the leech, Hirudo medicinalis, elicits withdrawal behavior that has two components: local bending in the segment stimulated and shortening in outlying segments. Local bending is characterized by excitation of longitudinal muscle on one side of the segment and inhibition on the other side. In shortening, all longitudinal muscles are excited. We wished to understand how these distinct motor patterns are produced by a nervous system with segmentally iterated neurons, a configuration that places some limitations on the complexity of connection patterns. 2. We searched for neurons in the segmental nervous system that subserved shortening behavior, expecting to find at least one interneuron in each segment that was involved in shortening behavior exclusively. We found instead that all interneurons involved in shortening are also involved in local bending, and no individual interneuron can completely account for shortening. 3. The motor output caused by individual identified interneurons is not entirely consistent with the shortening motor output pattern. For instance, one interneuron, cell 115, has the same pattern of motor effects from segment to segment, causing excitation of dorsal excitatory motor neurons and inhibition of ventral excitatory motor neurons. These effects would cause dorsal local bending, not shortening, in a few segments. Only one interneuron, cell 125, has motor effects that would cause shortening. 4. Individual interneurons were hyperpolarized while single sensory cells were stimulated, to quantify the contributions of individual interneurons to the observed motor pattern. Interneurons 115 and 125, and the inhibitory motor neuron, cell 1, were found to have significant roles in producing the shortening motor output. 5. A quantitative estimate of the role of each interneuron type showed that the identified interneurons account for most of the excitation of dorsal motor neurons, but for very little of the excitation of ventral motor neurons. This predicts that at least one additional interneuron type remains to be identified, one that would provide excitation to ventral motor neurons in several segments. 6. A back-propagation trained neural network model was constructed to predict the connections of the as yet unidentified interneurons. To match the known properties of interneurons, it was necessary to include a segmental similarity constraint in the training algorithm for segmentally iterated model neurons. The modeled networks predicted that there are at least two kinds of interneurons yet to be found. Also, the modeling showed that interneurons can have input and output patterns that differ very little from segment to segment but yet produce major differences in the motor output.


Author(s):  
Eve Marder

The crustacean stomatogastric nervous system has become one of the premier preparations used for the study of the mechanisms underlying the generation of rhythmic motor patterns. The stomatogastric ganglion (STG) contains about 30 neurons, most of which are motor neurons that innervate more than 40 sets of striated muscles that move the animal’s stomach. Descending projection neurons from the two commissural ganglia (CoGs) and the single oesophageal ganglion (OG) are important for the generation of the motor patterns produced by the STG. Identified sensory neurons project either into the CoGs to activate descending modulatory neurons, or directly into the STG.


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